How do genetics affect pancreatic cancer risk? Oncologist has an answer

New Delhi: Broadly the pancreatic cancer can be divided into the cancer arising from the tubes carrying the digestive juices from the pancreatic glands (called exocrine pancreas) into the segment of the small intestine called duodenum and this cancer is called Pancreatic Ductal Adenocarcinoma; the other, rarer type are the cancers arising from the endocrine cells residing in the pancreas (called islets of pancreas) such as alpha cells (secrete glucagon), beta cells (secrete insulin), delta cells (secrete somatostatin), and pancreatic polypeptide cells (secrete pancreatic polypeptide – PP). The cancers arising from the endocrine part of pancreas are clubbed as Neuro-endocrine tumours.

What are the risk factors of pancreatic cancer?

In an interaction with News9Live, Dr Thangarajan Rajkumar, Director of Research (Oncology), MedGenome, shared insights about pancreatic cancer, its risk factors and how palliative treatment comes to the rescue of patients.

“The major risk factors for pancreatic ductal adenocarcinoma are smoking, alcohol, obesity, chronic pancreatitis, and genetic factors. A family history of early onset (<50 years of age) pancreatic cancer is associated with a much higher risk of developing pancreatic cancer. Among the genes which have been shown to be altered in the germline (genes passed down by parents to their offsprings) and that can be associated with a much greater risk of developing pancreatic ductal adenocarcinoma include STK11 (screening to begin by 30 years of age or earlier), p16 (CDKN2A) (screening to begin by 40 years of age or earlier), BRCA1, BRCA2, TP53, ATM, PALB2, MLH1, MSH2, MSH6, and PMS2 (screening in those carrying a disease causing mutation in the other genes listed can start by 50 years or earlier); the last 4 genes cause mismatch DNA repair abnormalities and result in Lynch syndrome, which has large intestine cancers as well as cancers at other sites including pancreas. In addition, PRSS1 gene is known to be associated with hereditary pancreatitis and it is better they begin screening 20 years after pancreatitis or by 40 years of age,” explained Dr Rajkumar.

In individuals suspected to have a possible hereditary cancer, genetic counselling and then decision on gene testing using a panel of genes is advisable. In those with a pancreatic cancer and a germline mutation in one of the genes (the list will grow as more research is done), the first (parents, siblings, children) and second degree (grand-parents, grandchild, aunts, uncles, nephews and nieces) relatives can be offered predictive testing (once they are over 18 years of age), wherein only the disease-causing mutation identified is tested for.

Pancreatic cancer screening

At present screening in these high-risk individuals for pancreatic cancer will involve using Imaging modalities such as contrast-enhanced Magnetic resonance imaging (MRI), magnetic resonance cholangiopancreatography (MRCP) which evaluates the bile duct inside and outside the liver, gall bladder and pancreas and its ducts near the head of the pancreas. Using endoscopy guided ultrasound is another option.

Screening for pancreatic cancer in asymptomatic individuals is not advised especially if they are not of the high-risk group. A lot of research is happening to develop blood-based tests which if proven to be accurate, will be very useful.

Palliative care for pancreatic cancer

In those who develop pancreatic cancer, surgery is the best option if it is operable. Additional radiation and/or chemotherapy can improve outlook in the operated patients. For those considered inoperable, radiation and/or chemotherapy can be used. In individuals with metastatic disease, chemotherapy and targeted therapy can be tried. In patients with advanced disease and with mismatch DNA repair gene mutations or high tumour mutational burden, immune checkpoint therapy with Pembrolizumab can be given. Palliative treatment is important when cancer has spread and general condition is poor, with the focus on keeping the patient comfortable and pain-free.